Phenylphosphonium salts for treating hyperacidity or ulceration

ABSTRACT

PHENYLPHOSPHONIUM SALTS OF THIS INVENTION POSSESS USEFUL GASTRIC ANTISECRETORY, SPASMOLYTIC AND ANTIULCEROGENIC PROPERTIES. A METHOD OF TREATING GASTROINTESTINAL HYPERACIDITY AND ULCERAUON HAS ALSO BEEN DISCLOSED.

United States Patent 3,804,950 PHENYLPHOSPHONIUM SALTS FOR TREATINGHYPERACIDITY 0R ULCERATION Julius Diamond, Lafayette Hill, Pa., assignorto William H. Rorer, Inc., Washington, Pa.

No Drawing. Original application Jan. 22, 1972, Ser. No. 109,020, nowPatent No. 3,755,459. Divided and this application Jan. 8, 1973, Ser.No. 321,509

Int. Cl. A61k 27/00 US. Cl. 424-198 8 Claims ABSTRACT OF THE DISCLOSUREPhenylphosphonium salts of this invention possess useful gastricantisecretory, spasmolytic and antiulcerogenic properties. A method oftreating gastrointestinal hyperacidity and ulceration has also beendisclosed.

CROSS REFERENCE TO RELATED APPLICATIONS This is a division, ofapplication Ser. No. 109,020, filed Jan. 22, 1972, now U.S. Pat.3,755,459.

SUMMARY OF THE INVENTION This invention describes new phosphonium saltsand processes for their preparation. This invention further providesvaluable pharmaceutical preparations which contain these phosphoniumsalts as gastric antisecretory, spasmolytic, and antiulcerogenic agents.A method for the treatment of gastrointestinal hyperacidity andulceration is also described.

BACKGROUND OF THE INVENTION The pharmaceutical compositions which havebeen used as antisecretory and spasmolytic agents have been such asatropine, homatropine, propantheline bromide, dicyclomine hydrochlorideand other compounds which are structurally dissimilar to the onium saltsof this invention. Due to the anticholinergic properties of these knowncompounds, they produce undesirable side effects such as mydriasis,xerostomia, cyclopegia, and other unwanted effects.

There have been a number of aryl phosphonium salts described in theliterature. These have mainly been proposed for use as bactericidal andfungicidal agents, as well as plant growth regulators.

We have unexpectedly found novel phosphonium salts which have valuablepharmacologic properties.

We have found phosphonium salts which possess useful gastricantisecretory, spasmolytic and antiulcerogenic properties.

We have further found that the compounds of this invention aresubstantially void of the anticholinergic side efiects which accompanyheretofore known gastric antisecretory and spasmolytic agents.

We have also found a simple and effective method for treating gastrichyperacidity and gastrointestinal ulceration such as duodenal and pepticulcers.

DESCRIPTION AND PREFERRED EMBODIMENTS This invention provides a methodof preparing novel phosphonium salts.

This invention further provides pharmacologically active chemicalcompounds which are useful in treating gastrointestinal hyperacidity andulceration.

The compounds of this invention which are useful in treatinggastrointestinal hyperacidity and ulceration may be described by thegeneral Formula I:

3,804,950 Patented Apr. 16, 1974 ICC where Ar is an aryl or substitutedaryl group;

R, R and R" may be the same or diiferent and are a saturated orunsaturated acylic member having up to 12 carbon atoms, or a saturatedor partially unsaturated carbocyclic member having up to 12 carbonatoms; and

A* is a nontoxic inorganic or organic anion.

More specifically, the compounds of this invention may be described bythe structural Formula II:

@a- Y R 11 where:

where R, is hydrogen or loweralkyl;

R R R R and R may be the same or different and are hydrogen, halo,cyano, haloloweralkyl, nitro, haloloweralkoxy, haloloweracyl,haloloweralkylsulfonyl or halodiloweralkylsulfonamido; and

A- is a pharmacetuically acceptable nontoxic inorganic or organic anion(preferably chloride, bromide, iodide, sulfate, hydrogen sulfate,nitrate, phosphate, dihydrogenphosphate, monohydrogenphosphate, acetate,maleate, citrate, benzoate, lactate, benzenesulfonate, methanesulfonate,ethanesulfonate, etc.)

The more preferred compounds of this invention are also the morepreferred compounds which are useful in treating gastrointestinaldisorders and diseases and are described by the structural Formula II:

where X and Y are hydrogen, halo, haloloweralkyl, nitro orhaloloweralkoxy;

R, R and R" are a 5 to 12 carbon atom member which may be straightchained or branched and are alkyl or cycloalkyl;

R may also be arloweralkyl or substituted benzyl of the formula I RI! IRt- CH- a Ra where:

R, is hydrogen or lower alkyl;

R R R R and R are hydrogen, halo, haloloweralkyl, nitro orhaloloweralkoxy; and

A- is chloride, bromide, iodide, nitrate, phosphate or sulfate.

The most preferred compounds of this invention embrace those compoundsof structural Formula II where X and Y are hydrogen, fluoro, chloro,bromo, trifiuoromethyl, nitro or trifluoromethoxy;

R, R and R" are amyl, hexyl, heptyl, octyl, cycloamyl,

cyclohexyl, cycloheptyl or cyclooctyl;

R may also be benzyl or substituted benzyl of the formula where R, ishydrogen or methyl; and

R ,R R R and R are hydrogen, fluoro, chloro, bromo,

trifluoromethyl, nitro or trifluoromethoxy; and

A- is chloride, bromide or iodide.

A further more preferred embodiment of this invention embraces thosecompounds of Formula II where:

X and Y are hydrogen, halo, haloloweralkyl, nitro or haloloweralkoxy;

R' and R" are a 5 to 12 carbon atom member which may be straight chainedor branched and are: alkyl or cycloalkyl;

R is loweralkyl, loweralkenyl, loweralkynyl, cycloloweralkyl orcycloloweralkylloweralkyl;

A- is chloride, bromide, iodide, nitrate, phosphate or sulfate.

The more preferred compounds of this latter embodiment are exemplifiedwhere:

X and Y are hydrogen, fiuoro, chloro, bromo, trifluoromethyl, nitro ortrifluoromethoxy;

R and R" are amyl, hexyl, heptyl, octyl, cycloamyl,

cyclohexyl, cycloheptyl or cyclooctyl;

R is loweralkyl, loweralkenyl, loweralkynyl, cycloloweralkyl orcycloloweralkylloweralkyl;

A- is chloride, bromide or iodide.

In the descriptive portions of this invention, the following definitionsapply: The term lower alkyl" refers to a lower alkyl hydrocarbon groupcontaining from 1 to 5 carbon atoms which may be straight chained orbranched.

The lower alkoxy radical signifies an alkoxy group containing from 1 to5 carbon atoms which can be straight chained or branched.

The compounds of this invention can contain an asymmetric phosphorousatom when R R' k' Ar. For this reason, they may be obtained as racemicmixtures or as dextro and levorotatory insomers. These may be separatedby any of the various methods of resolution to obtain the d or 1compound. These isomers may also be obtained via stereospecificcondensation reactions. It is understood that the optical isomers ofthese compounds are embraced within the scope of this invention.

Representative compounds of this invention which are particularly usefulare as follows:

trioctylphenylphosphonium chloride trioctyl(p-fluorophenyl)phosphoniumchloride trioctyl(p-trifluoromethyl)phosphonium chloridedioctylbenzylphenylphosphonium chloride dioctyl(p-fluorobenzyl)phenylphosphonium chloridedioctyl(p-trifluoromethylbenzyl)phenylphosphonium chloridedioctylamylphenylphosphonium chloride dihexylamylphenylphosphoniumchloride dioctyl(p-bromobenzyl)phenylphosphonium bromidedioctyl(2,3,4,5,6-pentafiuorobenzyl) phenylphosphonium chloridetriheptylphenylphosphonium chloride trihexylphenylphosphonium chloridetricyclohexylphenylphosphonium chloride tricycloheptylphenylphosphoniumchloride diheptyl(2,6-dichlorobenzyl)phenylphosphonium chloridedioctyl(2,6-dichlorobenzyl) (p-chlorophenyl)phosphonium chloride dioctylu-methylbenzyl) (p-chlorophenyl) phosphonium chloridedihexylmethylphenylphosphonium chloride dihexylethylphenylphosphoniumchloride dihexylpropylphenylphosphonium chloridedihexyl(i-propyl)phenylphosphonium chloridedihexylbutylphenylphosphonium chloride dihexyl(i-butyl)phenylphosphoniumchloride dihexyl(s-butyl) phenylphosphonium chloridedihexyl(t-butyl)phenylphosphonium chloridedihexylpentylphenylphosphonium chloride dihexyloctylphenylphosphoniumchloride dihexylallylphenylphosphonium chloridedihexylmethallylphenylphosphonium chloridediheXyl(2-butenyl)phenylphosphonium chloride dihexyl(3-butenyl)phenylphosphonium chloride diheXyl(4-pentenyl)phenylphosphonium chloridedihexyl(2,4-pentadienyl) phenylphosphonium chloridedihexyl(2-propynyl)phenylphosphonium chloridedihexylcyclopropylphenylphosphonium chloridedihexylcyclopropylmethylphenylphosphonium chloridedihexylcyclopropylethylphenylphosphonium chloridedihexylcyclobutylphenylphosphonium chloridedihexylcyclobutylmethylphenylphosphonium chloridedihexylcyclopentylphenylphosphonium chloridedihexyl(2-cyclopentenyl)phenylphosphonium chloridedihexylpropargylphenylphosphonium bromidedihexyl(2-cyclohexenyl)phenylphosphonium chloridedihexylperfiuorobutylphenylphosphonium chloridedipentylallylphenylphosphonium chloride diheptylallylphenylphosphoniumchloride dicyclohexylallylphenylphosphonium chloridedicycloheptylallylphenylphosphonium chloridedicyclooctylallylphenylphosphonium chloridehexyloctylallylphenylphosphonium chlorideheptyloctylallyphenyphosphonium choridecyclohexyloctaylallylphenylphosphonium chloridecycloheptyloctylallylphenylphosphonium chloridecyclooctyloctylallylphenylphosphonium chloridetri-octyl(o-chlorophenyl)phosphonium chloride trihexy,l(m-chlorophenyl)phosphonium chloride trihexyl(p-chlorophenyl)phosphonium chloridetrihexyl(2,3-dichlorophenyl) phosphonium chloridetrihexyl(2,4-dichlorophenyl)phosphonium chloridetrihexyl(2,5-dichlorophenyl) phosphonium chloridetrihexyl(2,6-dichlorophenyl) phosphonium chloride triheXyl3,4-dichlorophenyl phosphonium chloride trihexyl 3,5 -dichlorophenylphosphonium chloride trihexyl(2-bromophenyl)phosphonium chloridetrihexyl(3-bromophenyl)phosphonium chloride trihexyl (4-bromophenyl)phosphonium chloride trihexyl (4-trifluoromethylphenyl) phosphoniumchloride trihexyl(4-nitrophenyl) phosphonium chloridetrihexyl(4-methoxyphenyl)phosphonium chloridedihexyl(o-chlorobenzyl)phenyl phosphonium chloridedihexyl(m-chlorobenzyl)phenyl phosphonium chloridedihexyl(p-chlorobenzyl)phenyl phosphonium chloridedihexyl(2,3-dichlorobenzyl)phenyl phosphonium chloridedihexyl(2,4-dichlorobenzyl)phenyl phosphonium chloridedihexyl(2,5-dichlorobenzyl)phenyl phosphonium chloridedihexyl(2,6-dichlorobenzyl)phenyl phosphonium chloridedihexyl(3,4-dichlorobenzyl)phenyl phosphonium chloridedihexyl(3,5-dichlorobenzyl)phenyl phosphonium chloridedihexyl(2,3,4-triehlorobenzyl) phenyl phosphonium chloridedihexyl(2,3,5-trichlorobenzyl) phenyl phosphonium chloridedihexyl(2,3,6-trichlorobenzyl)phenyl phosphonium chloridetriisoamylphenylphosphonium chloride tricyclopentylphenylphosphoniumchloride dipentylhexylphenylphosphonium chloride 7dipentylheptylphenylphosphonium chloridedipentylcyclohexylphenylphosphonium chloridediisoa'mylhexylphenylphosphonium chloridedipentylphenylbenzylphosphonium chloridediisoamylphenylbenzylphosphonium chloride.

The compounds of this invention may be prepared by the following generalprocedures:

Condensation of phosphorous trichloride with a molar amount of phenylorganometallic compound results in the phenyl dichlorophosphine. Furthercondensation with the proper organometallic reagents resultsin thetrisubstituted phosphine. Reaction of the trisubstituted phosphine withthe desired alkyl or aralkyl halide results in the correspondingquatenary phosphonium halide. [Phenyldichlorophosphines may also beprepared by the Michaelis modification of the Fridel-Crafts reaction asoutlined in JACS The following reaction equation illustrates thismethodof synthesis:

' Where X is chloride, bromide or iodide. When Xo'r Y is chloro,' then Xis brorno or iodo'but when X or Y is br omo, then X is iodo.

' Phosphonium compounds having two similar groups are prepared byreacting 'the phenyldichlorophosphine with 1 two moles of Grignardreagent followed by condensation with the desired halide."

. kR I @"R Y i i 11" The above reactions may be carried out by the usualsubstitution process for reactions involving organometal- 7 lie reagentswith halogen derivatives of'trivalent phosphorous compounds. g

One such method is by carrying out the reaction with one, two or threemoles of the desired organorntallid reagent (preferably a Grignardreagent) in an inertlme- 'dium such as ether, tetrahydrofuran, etc., andwith increased. temperatures. Isolation may be carried out either bysubjecting the reaction mixture to vacuum distillation or by giving themixture a hydrolytic treatment'with am- 75- moniac chloride solution,followed by distillation of the organic layer.

Preparation of the phosphonium salts is preferably carried out with thephenyldisubstituted phosphine and a halide of the formula RX where R andX' are as described above. The reaction is preferably carried out usinga solvent and with increased temperatures. These reactions are alsopreferably carried out in an inert ati mosphere under nitrogen or carbondioxide. The solvent used should be one that is miscible with thereactants and after it is convenient to use the reactant halide inexcess as the solvent or alternatively a high boiling polar medium suchas phenol, acetonitrile, dimethylformamide, dimethylsulfoxide,methylethylketone, etc. The reaction temperature may vary from roomtemperature with readily reactive reactants to about 250 C.,

although it is preferable to run the reaction at temperatures from about50 C. to C. The isolation of the desired phosphonium halide can becarried out by distilling off the solvent in vacuo and precipitating thephosphonium halide by the addition of a hydrocarbon liquid such asn-pentane, n-hexane, cyclohexane, etc.

Other anion salts can be produced by exchange of the halide with alkalior alkaline earth salts containing the appropriate anion.

When R is substituted benzyl, it is preferable to prepare thephosphonium compound on the phenyldisubstituted phosphine with thedesired benzyl halide.

R i I RI! This reaction is conveniently carried out on the benzylperatures. This synthesis is carried out and isolated as describedabove.

The benzyl halide starting materials can be conveniently prepared by thefollowing reactions.

R3 Ra Ra R:

R4- NH: R4 CN I g Ra Ra R5 Re b lrno+ Ills Illa Ra Ra n-ono R; -COOH RaRa Rs Ru (d) l (where Ra=loweralky1) (g) lLiAlH; R3 R: R: R2 I l m -o=oR4 CHz0H Rs a Ra Ra $41 R4 OHOH R4 CHzX' R5 Rs Ra Ra l l in -CHX 7Diazotization of an aromatic amine in the conventional manner followedby a Sandmeyer (a) type displacement produces the nitrile, which is thenhydrolyzed (b) to the carboxylic acid. Rosenmund reduction of thecarboxylic acid results in the aldehyde which in turn is interacted withthe desired alkyl Grignard reagent and oxidized (d) to obtain thea-alkylketone. This may then be reduced catalytically (e) to thea-alkylbenzyl alcohol. The alcohol is treated with a phosphoroustrihalide, phosphorous oxyhalide, phosphorous pentahalide, thionylhalideor sulfuryl halide reagent (f) to obtain the a-alkylbenzyl halide.Lithium aluminum hydride reduction of the benzoic acid (g) results inthe benzyl alcohol which is then treated as above (f) to obtain thebenzyl halide.

The phenyl Grignard reagents may be prepared from the correspondinganiline by conventional diazotization followed by a Sandmeyer typereaction using cuprous bromide or cuprous iodide to obtain the desiredphenyl halide which is then converted to the Grignard.

Appropriately desired end products having various X, Y, R R R R and Rsubstituents can be prepared at various stages of the synthesis of thestarting materials by using suitable reactions in order to convert onegroup to another. Thus, for example, using conventional methods, ahalogen group can be treated under Rosenmund von Brown conditions to thenitrile compound which in turn can be hydrolyzed to a carboxy. A nitrocan be reduced to an amino which can be alkylated to the dialkylaminosubstituent. A hydroxy compound can be prepared by demethylation of amethoxy substituent. A Sandmeyer type reaction can be carried out on anamino compound to introduce a chloro, bromo, xanthate, hydroxyl oralkoxyl group. The xanthate can then lead to the mercapto by hydrolysis,this turn can be alkylated to an alkylthio group which can be oxidizedto alkylsulfinyl and alkylsulfonyl groups.

We .have found that the compounds of this invention have usefulantiulcerogenic properties. Further, they have an effective degree ofgastric anti-secretory activity, i.e., they reduce the volume and theacidity of the gastric fluid in humans and mammals. Still further, thesecompounds produce a considerable spasmolytic action on thegastrointestinal musculature, i.e., they reduce the peristaltic actionof the gastrintestinal musculature which is manifested by a delay ingastric emptying time.

Until now, the known antiulcerogenic compounds which showed gastricanti-secretory and gastrintestinal spasmolytic action have included suchagents as atropine, homatropine, propantheline, dicyclomine, etc. Thesecompounds, however, cause accompanying undesirable anticholinergicproperties such as mydriasis, xerostomia, cyclopegia, etc.

We have found that the phosphonium compounds of this invention areparticularly useful as antisecretory, antispasmodic and antiulcerogenicagents because they are essentially devoid of these unwanted effects.

In particular, the phosphonium compounds, as herein described, areuseful in the treatment of such gastrointestinal disorders and diseasesas duodenal ulcer and peptic ulcer.

For all these purposes, the phosphonium compounds of this invention canbe administered orally or parenterally, but they are preferablyadministered orally. Orally, they may be administered as tablets,aqueous or oily suspension, dispersible powders or granules, emulsions,hard or soft capsules, or syrups or elixirs. The term parenteral,

as used herein, includes subcutaneous injection, intramuscular injectionor infusion techniques.

Compositions intended for oral use may be prepared according to anymethod known to the art for the manufacture of pharmaceuticalcompositions and such compositions may contain one or more agentsselected from the group consisting of sweetening agents, flavoringagents, coloring agents and preserving agents, in order to provide apharmaceutically elegant and palatable preparation.

Further, these compounds may be tableted or otherwise formulated so thatfor every 100 parts by weight of the composition, there are presentbetween 5 and parts by weight of the active ingredient. The dosage unitform will generally contain between about 1 mg. and about 500 mg. of theactive ingredients of this invention. The preferred unit dose is betweenabout 10 mg. and mg.

The dosage regimen in carrying out the methods of this invention is thatwhich insures maximum therapeutic response until improvement is obtainedand thereafter the minimum effective level which gives relief. Thus, ingeneral, the dosages are those that are therapeutically effective in thetreatment of ulcerogenic disease conditions or symptoms, such asduodenal and peptic ulcer. In general, the daily dose can be betweenabout 0.1 mg./kg. and 50 mg./kg. (preferably in the range of 1-25mg./kg./day). Bearing in mind, of course, that in selecting theappropriate dosage in any specific case, consideration must be given tothe patients weight, general health, age and other factors which mayinfluence response to the drug.

Various tests in animals have been carried out to show the ability ofthe compounds of this invention to exhibit reactions that can becorrelated with antiulcerogenic activity in humans. These tests involvesuch as the effects of the phosphonium compounds on gastric secretion,gastrointestinal spasm and their effect against ulcerogenic agents. Ithas been found that the compounds of this invention when tested in theabove variety of situations show a marked activity.

One such test is the gastric secretion test. This test is carried out asfollows: Shay rats are fasted for 4-8 hours, and water is given ad lib.The rats are selected at random and separated into groups of 10. Theanimals are treated intraduodenally (I.D.) with the test compound or thevehicle immediately subsequent to the ligation of the stomach at thepyloric sphincter. The animals are sacrificed with chloroform at 4 hourspost-drug administration, the stomach is removed and its contents areassayed for volume, pH and total acids.

A second gastric secretion test is carried out on dogs. This is outlinedin the Handbook of Physiology, Section 6: Alimentary Canal, vol. II:Secretion, American Physiology Society, Washington, DC, 1967.

It has been found that the compounds of this invention when subjected tothe above gastric secretion tests display a marked ability to decreasegastic volume and gastic acidity. These tests are known to correlatewell with gastric activity in humans and is a standard test used todetermine anti-secretory properties.

To determine the antiulcer effectiveness, the following test isemployed: Male Wistar rats (-150 grams) are fasted for 24 hours, thengiven reserpine at 5 mg./ kg. i.p. Twenty-four hours later, the stomachsare removed and examined for ulceration. Ulcers are graded on a O-4scale and the number of ulcers is recorded. Pretreatment with thephosphonium compounds of this invention produces a decrease in ulcergrade and the number of ulcers compared to the control reserpine-treatedrats.

Determination of anti-spasmodic properties can be carried out by theprocedure as outlined by D. A. Brodie and S. K. Kundrats in theirarticle entitled Effect of Drugs on Gastric Emptying in Rats, Fed. Proc.24:714 (1965).

Mydriasis isdetected by the procedure R. A. Turner, Screening Methods inPharmacology, Academic Press, New York, and London, pp. 174-5, 1965.Acute toxicity 9 is calculated according to the standardLitchfield-Wilcoxon procedure.

In view of the results of these tests, the pharmacological data clearlyindicates that the phosphonium compounds of this invention can beconsidered to be efiective antiulcerogenic, antisecretory, andantispasmodic agents which are substantially free of anticholinergicside elfects and having a low toxocity. I

The following are detailed examples which show the preparation of thecompounds of this invention. They are to be construed as illustrationsof said compounds and not as limitations thereof.

EXAMPLE 1 Phenyldichlorophosphine To 83 g. (0.6 mole) of phosphorustrichloride is added 27 g. (0.2 mole) of aluminum chloride and 13.8 g.(0.15 mole) of dry benzene. This reaction mixture is then gently heatedfor 2rhours with stirring overa blanket of nitrogen to expell the formedhydrogen chloride. The reaction mixture is then refluxed with vigorousstirring for an additional hour. The heat source is then removed andwhile the reaction mixture is still hot, phosphorus oxychloride 30.7 g.(0.2 mole) is gradually added. The mixture is then allowed to cool toroom temperature and extracted continuously with petroleum ether for 2hours. The petroleum ether extract is then concentrated. in vacuo anddistilled to obtain phenyldichlorophosphine.

, When benzene in the above example is replaced by the compounds ofTable I below and the reaction product is fractionated thenthecorresponding product of Table II below is prepared. 7

TABLE I Toluene Ethylbenzene Propylbenzene i-Propylbenzenet-Butylbenzene o-Xylene m-Xylene p-Xylene Biphenyl p-MethylbiphenylAnisole Phenetole m-Dimethoxybenzene' Trifiuoromethoxybenzene Phenylether o-Diethylbenzene TABLE II p-Tolyldichlorophosphinep-Ethylphenydichlorophosphine p-Propylphenyldichlorophosphinep-i-Propylphenyldichlorophosphine p-t-Butylphenyldichlorophospine 3,4-dimethylphenyldichloropho sphine(2,4-dimethylphenyl)dichlorophosphine2,5-dimethylphenyl)dichlorophosphine (p-Biphenyl)dichlorophosphine(p,p'-Methylbiphenyl)dichlorophosphine p-Methoxyphenyldichlorophosphinep-Ethoxyphenyldichlorophosphine 2,4-dimethoxyphenyldichlorophosphinep-Trifiuorornethoxyphenyldichlorophosphinep-Phe'noxyphenyldichlorophosphine 3,4-diethylphenyldichlorophosphine.

EXAMPLE 2 Dioctylphenylphosphine To a Grignard mixture ofn-octylmagnesium chloride (0.53 mole) prepared from 13.8 g. of magnesiumturnings and 78.4 g. of n-octyl chloride in 1300 ml. ether is added 31.2g. (0.175 mole) of 'phenyldichlorophosphine in 100 ml. of ether withvigorous stirring and in a nitrogen atmosphere at 0 C. The reactionmixture is allowed to warm to room temperature over 2 hours. The mixtureis then poured onto an ice-cold saturated solution of ammonium chloride(250 ml.) and the mixture stirred for an additional hour. The aqueouslayer is extracted with 2-150 ml. portions of ether which is thencombined with the ether layer, dried over sodium sulfate, evaporated todryness and distilled to obtain dioctylphenylphosphine.

When n-octyl chloride in the above reaction is substituted with thehalides of Table I below, then the corresponding product of Table 11below is prepared.

TABLE I n-Pentyl chloride n-Hexyl chloride n-Heptyl chloride n-Nonylchloride n-Decyl chloride n-Undecyl chloride n-Dodecyl chloride Isoamylchloride 2-methyl-1-butenyl chloride Cyclohex-Z-enyl chloride Cyclooctylchloride Cycloheptyl chloride Cyclopentyl chloride Cyclohexyl chlorideCyclohexylmethyl chloride 3,4,5-trimethylheptyl chloride 2-propylallylchloride 4-methyl-3-penten-1-yl chloride 2-methylheptyl chloride3-methylheptyl chloride 2-ethylhexyl chloride 2,2,3,3-tetramethylbutylchloride Cyclooct-2-enyl chloride Iso-octenyl chloride.

TABLE II Dipentylphenylphosphine DihexylphenylphosphineDiheptylphenylphosphine Dinonylphenylphosphine DidecylphenylphosphineDiundecylphenylphosphine DidodecylphenylphosphineDiisoamylphenylphosphine Di (Z-methyll-butenyl phenylphosphine Di-(cyclohex-Z-enyl phenylphosphine Dicyclooctylphenylpho sphine Dicycloheptylphenylpho sphine Dicyclop entylphenylphosphineDicyclohexylphenylphosphine Dicyclohexylmethylphenylphosphine Di- 3,4,5-trimethylheptyl )phenylphosphine Di- (2-propylallyl) phenylphosphine Di- (4-methyl-3 -penten-1-yl) phenylphosphine I Di-(Z-methylheptyl) phenylphosphine Di- (3 -methylheptyl phenylphosphineDi- (2-ethylhexy1) phenylphosphine Di- (2,2,3, 3 -tetramethylbutylphenylphosphine Di- (cyclooct-2-enyl) phenylphosphine Di- (iso-octenyl)phenylphosphine.

EXAMPLE 3 When phenyldichlorophosphine in Example 2, is replaced by thephosphines of Table II, Example 1, then the corresponding product ofTable I below is prepared.

TABLE I Dioctyl (p-tolyl) phosphine Dioctyl (p-ethylphenyl phosphineDioctyl p-propylphenyl )phosphine Dioctyl (p-i-propylphenyl pho sphineDioctyl (p-t-butylphenyl) phosphine 1 1 TABLE IContinued Dioctyl(3,4-dimethylphenyl phosphine Dioctyl (2,4-dimethylphenyl) phosphineDioctyl (2,5-dimethylphenyl) phosphine Dioctyl (p-biphenyl phosphineDioctyl (p,p'-methylphenyl phosphine Dioctyl (p-methoxyphenyl phosphineDioctyl (p-ethoxyphenyl phosphine Dioctyl( 2,4-dimethoxyphenyl)phosphine Dioctyl (p-trifluoromethoxyphenyl phosphine Dioctyl(phenoxyphenyl) phosphine Dioctyl 3,4-diethylphenyl phosphine.

EXAMPLE 4 When n-octylchloride in Example 2 is replaced with the halidesof Table I, Example 2 and when phenyldichlorophosphine is replaced withthe phosphines of Table II, Example 1, then the corresponding tertiaryphosphine is prepared. A representative list of the compounds preparedis shown below in Table I.

TABLE I Dipentyl (p-tolyl phosphine Dihexyl (p-tolyl pho sphine Diheptyl(p-tolyl) phosphine dinonyl (p-tolyl) phosphine Diisoamyl (p-tolyl)phosphine Di- (cyclohex-Z-enyl) p-tolyl) pho sphine Dicyclooctyl(p-tolyl phosphine Dicycloheptyl (p-tolyl phosphineDicyclohexyl(p-tolyl) phosphine Dicyclohexylmethyl (p-tolyl) phosphineDi- (2-propylallyl) (p-tolyl) phosphine Di- (iso-octenyl) (p-tolylphosphine Diheptyl (p-ethylphenyl phosphine Diheptyl (p-propylphenylphosphine Diisoamyl(p-methoxyphenyl phosphine Dicyclohex-Z-enyl)p-ethylphenyl phosphine Dicyclohexylmethyl p-t-butylphenyl pho sphineDinonyl(p-propylphenyl) phosphine Di- (Z-ethylhexyl)(2,5-dimethylpheny1) phosphine Dicycloheptyl (p-methoxyphenyl phosphineDiisoamyl(p-methoxyphenyl phosphine Di- (2,2,3 ,3-tetramethylbutyl)(p-tolyl phosphine Di- (2-methyll-butenyl) (p-tolyl) phosphine Didecyl(p-biphenyl phosphine Dipentyl (p-tolyl phosphine Di- (cyclooct-2-enyl)(2,5-dimethylphenyl) phosphine Dicyelohex-Z-enyl) (p-tolyl) phosphineDicyclohexylmethyl p-ethoxyphenyl) phosphine Dihexyl 3,4-diethylphenylphosphine Dicyclohexyl (2,4-dimethylphenyl pho sphine Di-(iso-octenyl)(p-ethoxyphenyl)phosphine Di- (2-propylallyl) (p-propylphenyl phosphineDicyclooctyl 3 ,4-dimethylphenyl phosphine Didodeeyl (p-phenoxyphenylphosphine Dicyclopentyl p-trifiuoromethoxyphenyl) phosphine Diheptyl(p,p'-methylbiphenyl) phosphine Di- 3,5 ,5trimethylheptyl) p-ethylphenylphosphine Di-(4-methyl-3-penten-1-yl) (p-tolyl phosphine Di-Z-methylheptyl) (p-methoxyphenyl phosphine Diundecyl(p,p'-methylbiphenyl) pho sphine Di- (3-methylhepty1) (p-tolyl)phosphine.

EXAMPLE 5 Phenyldichlorophosphine To a Grignard mixture ofphenylmagnesium bromide (0.192 mole) prepared from 5 g. of magnesiumturnings and 28.4 g. of bromobenzene in 600 ml. ether is added dropwisewith stirring 52.8 g. (0.384 mole) of phosphorus trichloride in 120 ml.of ether, in a nitrogen atmosphere at 0 C. The reaction mixture isallowed to warm to room temperature with stirring over 2 hours. Thisreaction mixture is filtered and the solid washed with 2-100 m1. ethercombined with the filtrate, concentrated in vacuo and distilled toobtain phenyldichlorophosphine.

When bromobenzene in the above example is replaced by the compounds ofTable I below, then the corresponding phosphine of Table II below isprepared.

TABLE I l-bromo-Z-chlorobenzene 1-bromo-3-chlorobenzene1-bromo-4-chlorobenzene 1-bromo-2,3-diehlorobenzene1-brom0-3,S-dichlorobenzene 2-bromo-1,4-dichlorobenzene4-bromo-1,2-dichlorobenzene 1-bromo-4-t-butylbenzene1-bromo-2,3-dimethylbenzene 1-bromo-2,4-dimethylbenzene4-bromo-1,2-dinitrobenzene 1-br0mo-2-ethoxybenzene1-bromo-4-ethoxybenzene 1-bromo-4-fluorobenzene 1-bromo-2-iodobenzene1-bromo-3-iodobenzene 1-bromo-4-iodobenzene 1-bromo-4-i-propylbenzene2-bromo-4-i-propy1-l-methylbenzene 1-brom0-2-methoxybenzene1-bromo-2-nitrobenzene 1-bromo-4-nitrobenzene 1-bromo-4-phenoxybenzene1-bromo-4-trifiuoromethylbenzene 1-bromo-4-trifiuoromethoxybenzene1-br0mo-4-biphenyl 1-bromo-4-phenoxybenzene 1-chloro-4-biphenyl1,4'-dichlorobiphenyl 1-chloro-4-methylbenzene1-chloro-2,4-diethylbenzene 1-iodo-2-methoxybenzene1-iodo-3-methoxybenzene 1-iodo-4-methoxybenzene 1-iodo-4-nitrobenzene1-iodo-2,4-dichlorobenzene 1-iodo-2,6-dichlorobenzene1-iodo-3,4-dichlorobenzene 1-iodo-4-trifluoromethylbenzene1-iodo-4-methylbenzene.

TABLE II (2-chlorophenyl dichloropho sphine (3 -chlorophenyl)dichlorophosphine (4-ehlorophenyl) dichlorophosphine (2, 3-dichlorophenyl) dichloropho s phine (3,5 -dichloropheny1dichlorophosphine (3 ,4dichlorophenyl) dichlorophosphine(4-t-butylphenyl dichlorophosphine (2,3 -dimethylphenyldichlorophosphine (2,4-dimethylphenyl dichlo ropho sphine (3,4-dinitrophenyl dichlorophosphine (2-ethoxyphenyl) dichlorophosphine(4-ethoxyphenyl) dichlorophosphine (4-fluoropheny1)dichlorophosphine(2-bromophenyl dichlorophosphine (3 -bromophenyl) dichlorophosphine(4-bromophenyl dichlorophosphine 4-i-propylphenyl )dichlorophosphine(2-methyl-5-i-propylphenyl) dichloropho sphine 2-methoxyphenyldichlorophosphine (2-nitrophenyl) dichlorophosphine (4-nitrophenyldichlorophosphine (4-phenoxyphenyl) dichlorophosphine(4-trifiuoromethylphenyl) dichlorophosphine (4-trifiuoromethoxypheny1)dichlorophosphine (4-biphenyl) dichlorophosphine (4-phenoxyphenyl)dichloropho sphine (4,4'-chlorobiphenyl) dichlorophosphine 13 TABLEIIContinued (4-methylphenyl) dichlorophosphine 2,4-diethylpheny1)dichlorophosphine (3-methoxyphenyl) dichlorophosphine (4-methoxyphenyldichloropho sphine (2,4-dichlorophenyl dichlorophosphine2,6-dichlorophenyl) dichlorophosphine.

EXAMPLE 6 Dihexylphenylphosphine To a Grignard mixture ofn-hexylmagnesium chloride (0.45 mole) prepared from 11.8 g. of magnesiumturnings and 54 of n-hexylchloride in l l. ether is added 31.2 g. (0.175mole) of phenyldichlorophosphine in 100 ml. of ether with vigorousstirring and in a nitrogen atmosphere at C. The reaction mixture isallowed to warm to room temperature for 3 hours. The mixture is pouredonto a saturated ice-bath solution of ammonium chloride and the mixturestirred for an additional half hour. The mixture is extracted threetimes with 300 ml. portions of ether. The ether is dried over sodiumsulfate, evaporated to dryness and fractionated to obtaindihexylphenylphosphine.

When phenyldichlorophosphine in the above example is replaced by thephenylphosphine of Table II, Example 5, then the corresponding productof Table I below is prepared.

TABLE I Dihexyl 2-chlorophenyl pho sphine Dihexyl 3-chlorophenyl)phosphine Dihexyl (4-chlorophenyl) phosphine Dihexyl (2, 3-dichlorophenyl) pho sphine Dihexyl (3 ,5 -dichlorophenyl) pho sphineDihexyl (3 ,4-dich1orophenyl pho sphine Dihexyl 4-t-butylphenyl) phosphine Dihexyl 2, S-dimethylphenyl) phosphine Dihexyl (2,4-dimethylphenylphosphine Dihexyl( 3,4-dinitrophenyl phosphine Dihexyl (2-ethoxyphenylphosphine Dihexyl (4-ethoxyphenyl phosphine Dihexyl (4-fluorophenyl)phosphine Dihexyl (2-bromophenyl pho sphine Dihexyl 3-bromophenylphosphine Dihexyl (4-bromophenyl)phosph1ne Dihexyl (4-i-propylphenyl)phosphine Dihexyl 2-methyl-5-i-propylphenyl )phosphine Dihexyl2-methoxyphenyl phosphine Dihexyl (2-nitrophenyl phosphine Dihexyl4-nitrophenyl )pho sphine Dihexyl 4-phenoxyphenyl) pho sphine Dihexyl(4-trifluororuethylphenyl phosphine Dihexyl 4-trifiuoro'methoxyphenyl)phosphine Dihexyl (4-biphenyl) phosphine Dihexyl (4-phenoxyphenylphosphine Dihexyl (4,4-chlorobiphenyl) phosphine Dihexyl 4-methylphenylphosphine Dihexyl 2,4-diethylphenyl) phosphine Dihexyl B-methoxyphenylphosphine Dihexyl 4-methoxyp henyl phosphine Dihexyl 2,4-dichlorophenylphosphine Dihexyl(2,6-dichlorophenyl phosphine.

EXAMPLE 7' Hexylphenylchlorophosphine To a Grignard mixture ofhexylmagnesium chloride (0.1 mole) prepared from (2.6 g. of magnesiumturnings and 16.3 g. of hexylbromide in 300 ml. of ether) is addeddropwise to an inert atmosphere with stirring and at 0 C., 43 g. (0.15mole) of phenyldichlorophosphine in 75 ml. of ether. The reactionmixture is stirred over 1% hours and allowed to gradually warm to roomtemperature. The reaction mixture is then filtered, residue washed withether combined with the filtrate and concentrated in vacuo and distilledto obtain hexylphenylchlorophosphine.

When hexylbromide in the above reaction is replaced phosphine of TableI, below is prepared.

TABLE I Pentylphenylchlorophosphine HeptylphenylchlorophosphineOctylphenylchlorophosphine NonylphenylchlorophosphineDecylp'henylchlorophosphine UndecylphenylchlorophosphineDodecylphenylchlorophosphine Isoamylphenylchlorophosphine(2-methyl-1-butenyl) phenylchlorophosphine (Cyclohex-Z-enylphenylchlorophosphine CyclooctylphenylchlorophosphineCycloheptylphenylchlorophosphine CyclopentylphenylchlorophosphineCyclohexylphenylchlorophosphine Cyc1ohexylrnethylphenylchlorophosphine(3 ,4,5-tri methylhepty1) phenylchlorophosphine (2-propylallylphenylchlorophosphine (4-methyl-3-penten-1-yl)phenylchlorophosphine(Z-methylheptyl) phenylchlorophosphine 3 -methylheptyl phenylchlorophosphine (Z-ethylhexyl phenylchlorophosphine 2,2,3,3-tetramethylbutylphenylchlorophosphine (Cyclooct-Z-enyl phenylchlorophosphine(Iso-octenyl phenylchlorophosphine.

EXAMPLE 8 When phenyldichlorophosphine of Example 7 is replaced with thephenyldichlorophosphines of Table II, Example 1 and Table II, Example 5,then the corresponding phosphines of Table I, below are prepared.

TABLE I Hexyl( 2-chlorophenyl chlorophosphine Hexyl(3-chlorophenyl)chlorophosphine Hexyl(4-chlorophenyl) chlorophosphine Hexyl2,3-dichlorophenyl chlorophosphine Hexyl 3 ,S-dichlorophenylchlorophosphine Hexyl 3 ,4-d ichlorophenyl chlorophosphine Hexyl(4-t-butylphenyl chlorophosphine Hexyl (2,3-dimethylphenylchlorophosphine Hexyl 2,4-di-methylphenyl chlorophosphine Hexyl3,4-dinitrophenyl chlorophosphine Hexyl Z-ethoxyphenyl chlorophosphineHexyl (4-ethoxyphenyl) chlorophosphine Hexyl (4-fluorophenylchlorophosphine Hexyl( 2-bron1ophenyl chlorophosphine Hexyl3-bromophenyl ch10 rophosphine Hexyl (4-bromophenyl) chlorophosphineHexyl (4-i-propylphenyl chlorophosphine Hexyl (2-methy1-S-i-propylphenylchlorophosphine Hexyl (Z-methoxyphenyl chlorophosphineHexyl(Z-nitrophenyl) chlorophosphine Hexyl (4-nitrophenylchlorophosphine Hexyl 4-phenoxyphenyl chlorophosphine Hexyl4-trifluoromethylphenyl chlorophosphine Hexyl (4-trifiuoromethoxyphenylchlorophosphine Hexyl(4-bipheny1) chlorophosphine Hexyl (4-phenoxyphenylchlorophosphine Hexyl (4,4-chlorobiphenyl chlorophosphine Hexyl(4-methylphenyl) chlorophosphine Hexyl 2,4-diethylphenyl chlorophosphineHexyl (3 -rnethoxyphenyl chlorophosphine Hexyl (4-methoxyphenylchlorophosphine Hexyl 2,4-dichlorophenyl chlorophosphine Hexyl2,6-dichlorophenyl chlorophosphine Hexyl (p-ethylphenyl chlorophosphineHexyl (p-propylphenyl chlorophosphine Hexyl (2,4-dimethylphenylchloropho sphine Hexyl 2,5 -di methylphenyl chlorophosphine Hexyl 3,4-diethylphenyl chlorophosphine.

1 EXAMPLE 9 When phenyldichlorophosphine of Example 7 is replaced withthe phenyldichlorophosphines of Table II, Example 1 and Table II,Example 5 and when hexyl chloride is replaced with the halides ofTable 1. Example 2, then the corresponding disubstituted phosphine isprepared. A representative list of the compounds prepared is shown inTable I, below.

TABLE I Pentyl (2-chlorophenyl chlorophosphine Heptyl(2-nitrophenylchlorophosphine Cyclooctyl( 2-bromophenyl chlorophosphineCyclohexyl(2-chlorophenyl) chlorophosphine (Z-methyll-butenyl)(Z-ethoxyphenyl chlorophosphine Cyclohexyl 3 ,5 -dicl1lorophenyl) chlorophosphine Cycloheptyl (2-methoxyphenyl chlorophosphineDecyl(3-methoxyphenyl) chlorophosphine Cyclohexyl 3 -bromophenyl) chloropho sphine Cyclohexyl (3 -chlorophenyl chlorophosphineCyclohex-Z-emyl) (4 methoxyphenyl chlorophosphine (Iso-octenyl)(4-phenoxyphenyl) chlorophosphine Pentyl 4-trifiuoromethylphenyl)chlorophosphine Cyclohexylmethyl 4-bromophenyl) chlorophosphine(Z-ethylhexyl) (4-t-buty1phenyl)chlorophosphine (Cyclooct-2-enyl)(4-ethoxyphenyl chlorophosphine Cycloheptyl (4-fluorophenyl chlorophosphine onyl 4-i-propylphenyl) chlorophosphine (Z-methylheptyl)(4-nitrophenyl) chlorophosphine cyclopentyl(4-chlorophenylchlorophosphine S-methylheptyl) (2,3-dimethylphenyl) chlorophosphineIsoamyl 2,3-dichlorophenyl chlorophosphine (4-methyl-3-pentenl-yl)(4-trifiuoromethoxyphenyl) chlorophosphine Undecy1( 4-methylphenylchlorophosphine Isoamyl( 3,4-diethylphenyl chlorophosphine Cyclohexyl(2,4-dimethylphenyl chlorophosphine (2,2,3,B-tetramethylbutyl)(4-phenoxyphenyl) chlorophosphine (2-propylallyl) (4-biphenyl)chlorophosphine Cyclohexyl(3,4-dich1orophenyl)chlorophosphineCyclohexylmethyl( 2,4-diethylphenyl) chlorophosphine Isoamyl2,5-dimethylphenyl chlorophosphine Cyclopentyl( 2,4-dimethylphenylchlorophosphine Dodecyl(2-methyl-S-i-propylphenyl) chlorophosphineIsoamyl ppropylphenyl) chlorophosphine Pentyl (2,6-dichlorophenyl)chlorophosphine Cyclohexyl (2,4-dichlorophenyl chlorophosphine (3,4,5-trimethylheptyl) (3,4-dinitrophenyl) chloropho sphine Cyclohexyl (4,4'-chlorobiphenyl) chlorophosphine.

EXAMPLE Hexyloctylphenylphosphine To a Grignard mixture ofoctylmagnesium bromide (0.075 mole) in 250 ml. of ether is addeddropwise with stirring 28.5 g. (0.125 mole) ofhexylphenylchlorophosphine in 75 ml. of ether at 0 C. The reaction iscarried out under nitrogen and vigorously stirred for 2 hours. Thetemperature is allowed to gradually warm up to room temperature. Thereaction mixture is then poured onto an ice-cold saturated solution ofammonium chloride (300 ml.) and the mixture stirred for one hour. Theaqueous layer is extracted with 200 ml. of ether combined with the etherlayer, dried over sodium sulfate, evaporated to dryness and distilled togive hexyloctylphenylphosphine.

When the octylmagnesium bromide of the above reaction is replaced withthe Grignard reagents of the halides of Table 1, Example 2, then thecorresponding tertiary phosphine of Table I below is prepared.

Pentylhexylphenylphosphine DihexylphenylphosphineHeptylhexylphenylphosphine NonylhexylphenylphosphineDecylhexylphenylphosphine UndecylhexylphenylphosphineDodecylhexylphenylphosphine IsoamylhexylphenylphosphineZ-methyll-butenyl) hexylphenylphosphine(Cyclohex-Z-enyl)hexylphenylphosphine CyclooctylhexylphenylphosphineCycloheptylhexylphenylphosphine CyclopentylphenylphosphineCyclohexylhexylphenylphosphine Cyclohexylrnethylhexylphenylphosphine(3,4,5-trimethylheptylhexylphenylphosphine(2-propylallyl)hexylphenylphosphine(4-methyl-3-penten-l-yl)hexylphenylphosphine(Z-rnethylheptyl)hexylphenylphosphine(3-methylheptyl)hexylphenylphosphine (2-ethylhexyl) hexylphenylphosphine (2,2,3,3-tetramethylbutyl)hexylphenylphosphine(Cyclooct-2-enyl)hexylphenylphosphine Iso-octenylhexylphenylphosphine.

EXAMPLE 11 When hexylphenylchlorophosphine of Example 10 is replaced bythe chlorophosphines of Table I, Example 7, then the correspondingtertiary phosphine of Table I below is prepared.

TABLE I EXAMPLE 12 When hexylphenylphosphine of Example 10 is replacedby the chlorophosphines of Table I, Example 8, then the correspondingtertiary phosphine of Table I, below is prepared.

TABLE I Octylhexyl(2-chlorophenyl phosphine Octylhexyl3-chlorophenyl)phosphine Octylhexyl (4-chlorophenyl) phosphineOctylhexyl (2,3-dichlorophenyl phosphine Octylhexyl (3 ,5-dichlorophenyl )phosphine Octylhexyl 3 ,4-dichlorophenyl) pho sphineOctylhexyl 4-t-butylphenyl) phosphine Octylhexy 2, 3 -dimethylphenylphosphine Octylhexyl 2,4-dimethylphenyl phosphine Octylhexyl 3,4-dinitrophenyl phosphine Octylhexyl 2-ethoxyphenyl) phosphineOctylhexyl 4-ethoxyphenyl) pho sphine Octylhexyl 4-fluorophenylphosphine Octylhexyl (2-bromophenyl phosphine Octylhexyl 3-bromophenylphosphine Octylhexyl (4-bromophenyl phosphine Octylhexyl(4-i-propylphenyl phosphine 1 7 i TABLE I-Contin-ued Octylhexyl(Z-methyl-S-i-propylphenyl) phosphine Octylhexyl 2-methoxyphenylphosphine Octylhexy1(2-nitrophenyl)phosphine Octylhexyl 4-nitrophenyl)phosphine Octylhexyl 4-phenoxyphenyl) phosphine Octylhexyl(4*tri-fluoromethylphenyl) phosphine Octylhexyl(4-trifluoromethoxyphenyl) pho sphine Octylhexyl 4-biphenyl) phosphineOctylhexyl (4-phenoxyphenyl phosphine Octylhexyl (4,4'-chlorophenylphosphine Octylhexyl (4-methylphenyl phosphine Octylhexyl2,4-diethylphenyl pho sphine Octylhexyl 3 -methxyphenyl phosphine Octylhexyl (4-methoxyphenyl phosphine Octylhexyl (2,4-dichlorophenyl phosphine Octylhexyl (2, 6-dichlorophenyl phosphineOctylhexy1(p-ethylphenyl)phosphine Octylhexyl p-propylphenyl )phosphineOctylhexyl (2-methy1-4-bromophenyl pho sphine Octylhexyl (2,S-dimethylphenyl) phosphine Octylhexyl (p-bromophenoxyphenyl) phosphine.

EXAMPLE 13 When octylmagnesium bromide of Example is replaced by theGrignard reagent of the halides of Table I, Example 2 andhexylphenylchlorophosphine is replaced by the chlorophosphines of Table1, Example 9', then the corresponding representative tertiary phosphinesof Table I below are prepared.

TABLE I Pentyl(Z-chlorophenyl) hexylphosphine Pentyl(3-chlorophenyl)hexylphosphine Pentyl (4-chlorophenyl) hexylphosphinePentyl(2,3-dichlorophenyl) hexylphosphine Pentyl( 3 ,5 -dichlorophenylhexylpho sphine Pentyl 3 ,4-dichlorophenyl hexylphosphinePentyl(4-t-buty1phenyl) hexylphosphine Pentyl(2,3-dimethylphenyl)hexylphosphine Pentyl(2,4-dimethylphenyl hexylphosphine Pentyl(3,4-dinitrophenyl hexylphosphine Pentyl (2-ethoxyphenyl)hexylphosphinePentyl(4-ethoxyphenyl) hexylphosphinePentyl(4-fluoropheny1)hexylphosphine Pentyl(2-bromophenyl)hexylphosphine Pentyl(3-bromophenyl) hexylphosphine Pentyl(4-bromophenyl)hexylphosphine Pentyl (4-i-propylphenyl) hexylphosphinePentyl( Z-methyl-S-i-propylphenyl) hexylphosphine Pentyl(Z-methoxyphenyl hexylphosphine Pentyl(2-nitropheny1)hexylphosphinePentyl (4-nitrophenyl hexylphosphine Pentyl (4-phenoxyphenyl)hexylphosphine Pentyl(4-trifluoromethylphenyl )vhexylphosphine Pentyl(4-trifluoromethoxy-phenyl) hexylphosphine Pentyl (4-biphenylhexylphosphine 'Pentyl(4-phenoxyphenyl) hexylphosphine Pentyl(4,4'-chlorobiphenyl) hexylphosphine Pentyl(4-methylphenylhexylphosphine Pentyl (2,4-diethylphenyl)hexylphosphinePentyl(3-methoxyphenyl)hexylphosphine Pentyl(4-meth0xyphenyl)hexylphosphine Pentyl(2,4-dichlorophenyl) hexylphosphinePentyl(2,6-dichlorophenyl) hexylphosphine Heptyl (2-nitrophenylisoamylpho sphine Cyclooctyl (2-brornophenyl pentylphosphineCyclohexyl(2-chlorophenyl)undecylphosphine (2-methyl-1-butenyl)(2-ethoxyphenyl) (2-ethylhexyl) phosphine Cyclohexyl(3,S-dichlorophenyl) hexylphosphine Cycloheptyl(Z-methoxyphenyl)(3-methylheptyl) phosphine Decyl(3-methoxyphenyl) phosphine Cyclohexyl(3-bromophenyl) pentylphosphine Cyclohexyl(3-chloropheny1)(cyclohex-z-enyl) phosphine (Cyclohex-Z-amyl) 4-methoxyphenyl )phosphine(Iso-octenyl) (4-phenoxyphenyl) cyclooctylphosphine Isoamyl(4-trifluoromethylphenyl) (2-methyl-1-butenyl) phosphineCyclohexylmethyl(4-bromophenyl) (Lmethylheptyl) phosphine (Z-ethylhexyl)(4-t-'butylphenyl)heptylphosphine (Cyclooct-Z-enyl) (4-ethoxyphenyl)(4-methyl-3-penten- 1- yl)phosphine Cyclohetpyl (4-fluorophenylisoamylphosphine Nonyl (4-i-propylphenyl) octylphosphine(Z-methylheptyl) (4-nitrophenyl cycloheptylphosphine Dicyclopentyl(4-chlorophenyl phosphine (3-methylhepty1) 2,3-dimethylphenylisoamylphosphine Isoamyl 2,3 -dichlorophenyl cyclohexylphosphine(4-methyl-3 -penten-1-yl) (4-trifluoromethoxyphenyl)cyclohexylmethylphosphine Undecyl (4-methylphenyl nonylphosphineIsoamyl(4-i-propylpheny1)phosphine Cyclohexyl (2,4-dimethylphenyldecylphosphine (2,2,3,3-tetramethylbutyl) (4-phenoxyphenyl)cyclohexylphosphine (2-propylallyl) (4-biphenyl) dodecylphosphineCyclohexyl(3,4-dichlorophenyl) (2,2,3,3-tetrarnethylbutyl)phosphineCyclohexylmethyl(2,4-diethylphenyl)isoamylphosphineIsoamyl(2,5-dimethylphenyl) (3,4,5 -trimethylheptyl) phosphineCyclopentyl(2,4-dimethylphenyl) (2-propylallyl) phosphine Dodecyl(2-methy1-S-i-propylphenyl cyclohexylphosphine Isoamy1(p-propylpheny1)(cyclooct-Z-enyl phosphine Cyclohexyl (2, 6-dichlorophenylisoamylphosphine Cyclohexyl (2,4-dichlorophenyl) iso-octenyl phosphine(3,4,5-trimethylheptyl) (3,4-dinitrophenyl)pentylphosphine Cyclohexyl4,4'-chlorobiphenyl) isoamylphosphine.

EXAMPLE 14 Hexyloctylpentylphenylphosphonium chloride To 76.5 g. (0.25mole) of hexyloctylphenylphosphine in 500 ml. of acetonitrile is added28.6 g. (0.27 mole) of pentyl chloride. The mixture is refluxed for 15hours, concentrated in vacuo and the residue agitated with 3-200 ml.portions of hexane. The hexane is evaporated to givehexyloctylpentylphenylphosphonium chloride.

When the procedure is followed but pentyl chloride is substituted forthe halides of Table I below, then the corresponding product isprepared.

TABLE I Methyl iodide Ethyl bromide Propyl bromide i-Propyl bromideButyl bromide i-Butyl chloride Sec-butyl chloride t-Butyl bromide Allylbromide Methallyl chloride 1-Bromo-2,4-pentadiene Z-Butenyl bromide4-Pentenylbromide l-Propynyl chloride Propargyl bromide S-hexynylchloride Cyclohex-Z-enylmethyl chloride 1-Bromo-2,4-cyclopentadieneCyclopropyl bromide Cyclobutylbromide Z-methylcyclopropyl bromide 1 9TABLE IContinued Cyclopropylmethyl chloride 2-ethylcyclopropylmethylchloride Cyclobutylmethyl bromide Pentafluoroethyl chloride5,5,5-trifluoro-l-bromopentane 3,3,3-trifluoro-l bromopropane.

EXAMPLE When the procedure of Example 14 is followed but pentyl chlorideis replaced by the halides of Table I, Example 2 and Table 1, Example 14and the hexyloctylphenylphosphine is replaced by the tertiary phosphinesof Examples 2, 3, 4, 6, 10, ll, 12 and 13, then the correspondingphosphonium salt is prepared. A representative list of the phosphoniumsalts prepared is shown in Table 1, below.

TABLE I Dipentylcyclohexylphenylphosphonium chlorideDihexylpentylphenylphosphonium chloride Diheptyl-i-amylphenylphosphoniumchloride Trinonylphenylphosphonium chloride Tridecylphenylphosphoniumchloride Diisoamylhexylphenylphosphonium chlorideDicycloheptylheptylphenylphosphonium chlorideDicyclopentylcycloheptylphenylphosphonium chlorideDicyclohexyl(Z-ethylhexyl) phenylphosphonium chlorideDicyclohexylmethyl(t-butyl) phenylphosphonium bromideDi-(Z-propylallyl)methylphenylphosphonium iodide Di-( 4-methyl-3-penten-1-yl) (4-pentenyl) phenylphosphonium bromide Di-(cyclooct-Z-enyl)methylphenylphosphonium iodideDi-(iso-octenyl)ethylphenylphosphonium bromide Trioctyl(p-tolyl)phosphonium chloride Dioctyl(i-propyl) (p-ethylphenyl) phosphoniumbromide Dioctyl( 3-methylheptyl) (p-bromophenyl phosphonium chlorideDioctylallyl(p-chlorophenyl)phosphonium bromideDioctylallyl(p-nitrophenyl) phosphonium bromide Dioctyl(2-propylallyl)(2-methyl-4- bromophenyl)phosphonium chloride Dioctylcyclopropylmethylp-biphenyl) phosphonium chloride Dioctyl( S-hexynyl) (p-methoxyphenylphosphonium chloride Dioctylhexyl(phenoxyphenyl)phosphonium chlorideDipentyl-t-butyl(p-chlorophenyl)phosphonium bromideDihexylallyl(pchlorophenyl) phosphonium bromide Diheptyl-i-propyl(p-chlorophenyl phosphonium bromideDiisoamylhexyl(p-chlorophenyl)phosphonium chloride Dicycloheptyl-i-amyl(p-chlorophenyl) phosphonium chloride Dicyclohexylhexyl (p-chlorophenylphosphonium chloride Dihexylpropargylphenylphosphonium bromideDicyclohexylmethyl (hexyl) (p-chlorophenyl) phosphonium chlorideDi-(2-propylallyl)-i-butyl(p-chlorophenyl)phosphonium chlorideDiheptylhexyl(p-tolyl) phosphonium chlorideDiheptylarnyl(p-nitrophenyl)phosphonium chlorideTriisoamyl(p-methoxyphenyl)phosphonium chloride Tricyclohexylmethylp-bromophenyl phosphonium chlorideTricycloheptyl(p-trifluoromethylphenyl)phosphonium chlorideDiisoamylhexyl(p-rnethoxyphenyl)phosphonium chloride Tripentyl (p-tolyl)phosphonium chloride Trihexyl(p-bromophenyl)phosphonium bromideTricyclopentyl(p-trifiuoromethoxyphenyl)phosphonium chlorideHeptyl(p,p'-chlorobiphenyl)phosphonium chloride 20 Di- Z-methylheptylhexyl p-methoxyphenyl) phosphonium chlorideDihexyloctyl(2-chlorophenyl)phosphonium chlorideDihexylpentyl(3-chlorophenyl)phosphonium chlorideDihexylpentyl(4-chlorophenyl)phosphonium chloride Dihexylpentyl(2,3-dichlorophenyl phosphonium chloride Trihexyl(3,5-dichlorophenyl)phosphonium chloride Dihexylheptyl(3,4-dichlorophenyl)phosphoniumchloride Dihexylisoamyl(4-t-butylphenyl)phosphonium chloride Dihexyl propyl 2,4-dimethylphenyl) phosphonium bromideDihexylmethallyl(Z-ethoxyphenyl) phosphonium chlorideTrihexyl(4-ethoxyphenyl)phosphonium chloride Trihexyl(4-fluorophenyl)phosphonium chloride Dihexylcyclopropyl(2-bromophenyl)phosphoniumbromide Dihexylcyclobutylmethyl 3-bromophenyl) phosphonium bromideDihexyloctyl(4-bromophenyl)phosphonium chloride Dihexyl-i-propyl (4-ipropylphenyl) pho sphonium bromideTrihexyl(2-methyl-5-i-propylphenyl)phosphonium chloride Dihexyl(2,4pentadienyl) 2-methoxyphenyl) phosphonium bromideDihexylmethallylphenylphosphonium chloride Dihexylheptyl(Z-nitrophenyl)phosphonium chloride Trihexyl(4-nitrophenyl)phosphonium chlorideTrihexyl(4-phenoxyphcnyl)phosphonium chlorideDihexyl(3,3,3-trifiuoropropyl) (4-trifluoromethylphenyl)phosphoniumbromide Trihexyl (4-biphenyl) phosphonium chloride Dihexyl-t-butyl(4-methylphenyl) pho sphonium bromide Dihexylethyl 2,4-diethylphenyl)phosphonium bromide Dihexylcyclobutyl 3 -methoxyphenyl phosphoniumbromide Trihexyl(4-methoxyphenyl) phosphonium chlorideTrihexyl(2,4-dichlorophenyl)phosphonium chlorideTrihexyl(2,6-dichlorophenyl)phosphonium chloridePentylheptylhexylphenylphosphonium chlorideDihexyl-t-butylphenylphosphonium chlorideHeptylhexylmethallylphenylphosphonium chlorideNonylhexylallylphenylphosphonium chlorideDecylethylhexylphenylphosphonium chlorideUndecylcyclopropylhexylphenylphosphonium chlorideDihexyldodecylphenylphosphonium chlorideIsoamylethylhexylphenylphosphonium chloride (2-methyl-1-butenyl)-i-propylhexylphenylphosphonium bromide (Cyclohex-Z-enyl)pentylhexylphenylpho sphonium chlorideCyclooctylheptylhexylphenylphosphonium chlorideCycloheptylpentylhexylphenylphosphonium chlorideCyclopentylpentylhexylphenylphosphonium chlorideDicyclohexylhexylphenylphosphonium chlorideDicyclohexylmethylhexylphenylphosphonium chloride(3,4,5-tri-methylheptyl)methylhexylphenylphosphonium iodide(2-propylallyl)hexylmethylphenylphosphonium iodide(4-methyl-3-penten-l-yl)hexylpentylphenylphosphonium chlorideDihexyl(Z-butenyl)phenylphosphonium bromide(Z-methylheptyl)hexylisoamylphenylphosphonium chloride 3-methylheptyl)hexyl (2-propylallylphenylpho sphonium chloride(2-ethylhexylhexyl)cyclohexylphenylphosphonium chloride(2,2,3,3-tetramethylbutyl)hexylpropylphenylphosphoniurn bromide 21ITABLE I-"Oon't'inired I (Cyclooct-Z-enyl)hexylisoamylphenylphosphoniumchloride V j Iso octenylhexylcyclohexylphenylphosphonium chloride 1Octylpentylisoamylphenylphosphoniurn chloride IOctylcyclopentylheptylphenylphosphonium chlorideDioctylmethylphenylphosphonium chloride I yDioctylisoamylphenylphosphonium chlorideOctyl(2-methyl-l-bntenyl)propylphenylphosphoninm v bromide Ovtyl(cycloheX-Z-enyl) -i-butylphenylphosphonium chloride jOctylcyclooctyl(iso-octenyl)phenylphosphonium chlorideOctylcyclopentylpropargylphenylphosphonium chlorideOctylmethylcycloh'exylmethylphenylphosphonium iodidectyl(2-propylallyl)propargylphenylphosphoninm chlorideDioctyl(4-methy1-3-penten-1-yl)phenylphosphonium chloride N voctylhexylpropyl(4-chlorophenyl)phosphonium bromideOctylhexyl(2-ethylhexyl(2,3-dichlorophenyl)phospho-t. nium chloride VOctylhexyl-t-butyl(4-t-butylphenyl)phosphonium chlorideOctylhexylpropynyl(2,3-dimethylphenyl)phosphonium chloride YOctylhexylcyclobutylmethyl(2,4-dimethylphenyl)phos- I phonium chlorideOctylhexylmethyl(2-ethoxyphenyl) phosphonium iodideOctylhexylpentafluoroethyl(4-fluorophenyl)phosphonium chlorideOctylhexyl-i-butyl(2 bromophenyl)phosphonium chlorideDioctylhexyl(4-bromophenyl)phosphonium.chlorideOctylhexyl(2,4-cyclopentadien-l-yl) (4-i-propylphenyl) phosphoniumchloride Octylhexylcyclobutyl(2-methoxyphenyl) phosphonium chloride V. tt Octylhexyl(Z-methylcyclopropyl) (4-nitrophenyl)phosphonium chlorideoctylhexylpropyl(4-trifluoromethylphenyl)phosphonium bromide r rDihexyl(2,4-cyclopentadien-1-yl)phenylphosphonium bromideOctylhexyl(2-ethylhexyl) (4-methoxyphenyl)rihosnhonium chloride V VOctylhexylcyclohexyl(2,4-dichloropheny1)phosphonium Y chloride r J-OctylheXyl-i-propyl(p-propylphenyl)phosphonium bromide v r 1Pentyl-i-propyl(2-chlorophenyl)hexylphosphonium Y bromide rPentyl-i-propyl(4-chlorophenyl)hexylphosphonium bromidePentylisoamyl(3,5-dichlorophenyl)hexylphosphonium chloride 1 t vPentyl-t-butyl(3,4-dichlorophenyl)hexylphosphonium bromide @VPentyl(pentenyl) (4-t-butylphenyl)hexylphosphonium chloride I H" j IPentyl(Z-methylcyclopropyl) (2 ,4-di methylphenyl.)hexylphosphoniumchloride Dipentyl (4-ethoxyphenyl)hexylphosphonium' chloridePentylpropyl(4-fluorophenyl)hexylphosphoniumbromidePentyl-sec-butyl(Z-bromophenyl)hexylphosphonium. chloride I jDipentyl(4-i-propylphenyl)hexylphosphonium chloridePentylisoamyl(4-nitrophenyl)hexylphosphoninm chloridePentylmethyl(4-triflnoromethylphenyl)hexylphosphonium iodide v tPentyl(cyclohex-Z-enylmthyl) (4-methylphenyl) hexylv phosphoniumchloride Penty(2-ethylcyclopropylmethyl) (4-methoxyphenyl) vhexylphosphonium chloride a -1Dipentyl(2,4-dichl0rophenyl)hexylphosphonium' chloridePenty1(3,3,3-trifluoropropyl) 2,-6 .-dichlorophenyl)hexyl .1

phosphonium chloride Dicyclooctyl(2-bromophenylpentylphosphoniumchloride (Z-methyl-l-butenyl) (Z-ethylcyclopropylmethyl) (2-ethoxyphenyl) (2-ethylhexyl)phosphonium chloride chloride Dicyclohexyl(3 -bromophenyl pentylphosphonium chloride (Cyclohex-Z-enyl ethyl(4-methoxyphenyl phosphonium bromide Diisoamyl(4-trifluoromethylphenyl)(Z-methyl-l-butenyl) phosphonium chloride IDicyclohexylmethyl(4-bromophenyl) (2-methylheptyl) phosphonium chloride(Z-ethylhexyl) propyl (4-t-butylphenyl) heptylphosphonium bromideDihexylcyclopropylphenylphosphonium bromide Allyl (cyclooct-2-enyl)(4-ethoxyphenyl) (4-methyl-3- penten-l-yDphosphonium bromideCycloheptyl(4-fluorophenyl)isoamylphosphonium chloride (Z-methylheptyl)cyclopropyl (4-nitrophenyl) cycloheptyl phosphonium chlorideDiisoamyl(3,4-diethylphenyl)phosphonium chloride(2,2,3,3-tetramethylbutyl)isoamyl(4-phenoxyphenyl) cyclohexylphosphoniumchloride (Z-propylallyl) a1lyl(4-biphenyl) do decylphosphonium chlorideIsoamyl(2,5-dimethylphenyl)pentyl(3,4,5-trimethylhepty1)phosphoniumchloride Cyclopentylmcthyl(2,4-dimethylphenyl) (2-propylallyl)phosphonium chloridelsoamyl(p-propylphenyl)hexyl(cyclooct-2-enyl)phosphonium chlorideCyclohexylhexyl(2,6-dichlorophenyl)isoamylphosphonium chlorideCyclohexyl(2,4-dichlorophenyl)isoamyl(iso-octenyl) phosphonium chloride(3,4,5 -trimethylheptyl) (2-ethylhexyl) (3,4-dinitrophenyl)pentylphosphonium chloride Tripentylphenylphosphonium chlorideTrihexylphenylphosphonium chloride Triheptylphenylphosphonium chlorideTrioctylphenylphosphonium chloride Triisoamylphenylphosphonium chlorideTricyclopentylphenylphosphonium chloride Tricyclohexylphenylphosphoniumchloride Tricycloheptylphenylphosphonium chlorideDipentylhexylphenylphosphonium chloride Dipentylheptylphenylphosphoniumchloride Dipentyloctylphenylphosphonium chlorideDihexylpentylphenylphosphonium chlorideTricyclohexylmethylphenylphosphonium chloride Tri-('3,4,S-trimethylheptylphenylphosphonium chloride wDihexyl(4-pentenyl)phenylphosphonium bromideTri-(2-propylallyl)phenylphosphonium chloride'Tri-(4-methyl-3-penten-1-yl)phenylphosphonium chloride ITri-(Z-mthylhptyl phenylphosphonium chloride Tri- 3 -methylheptyl)phenylphosphonium chloride Tri-(2-ethylhexyl)phenylphosphonium chlorideTri-(2,2,3,3-tetramethylbutyl)phenylphosphonium chloride Tri-(cyclooct-Z-enyl) phenylphosphonium chloride Tri- (iso-octenyl)phenylphosphonium chloride.

EXAMPLE l6 Dihexyl (p-trifluoromethylbenzyl)phenylphosphonium chlorideDidodecylphenylbenzylphosphonium chloride to obtaindihexyl(p-trifluoromethylbenzyl)phenylphosphonium chloride. 7

When p-trifiuoromethylbenzyl chloride in the above example issubstituted by the benzyl halides of Table. I below, then thecorresponding product is prepared.

TABLE I Benzyl bromide Benzyl chloride Benzyl iodidep-Trifluoromethoxybenzyl chloride.

p-Trifiuorooctylbenzyl chloride o-Trifluoromethylbenzyl chloridep-Trifiuoromethylsulfonylbenzyl chloride o-Chlorobenzyl chloridem-Chlorobenzyl chloride p-Chlorobenzyl chloride 2,3-dichlorobenzylchloride 2,4-dichlorobenzyl chloride.

2,5-dichlorobenzyl chloride 2,6-dichlorobenzyl chloride3,4-dichloroberizyl chloride 3,5-dichlorobenzyl chloride2,3,4-trichlorobenzyl chloride 2,3,5-trichlorobenzyl chloride2,3,6-trichlorobenzyl chloride 3,4,5-trichlorobenzyl chloridep-Ditrifiuoromethylsulfonylbenzyl chloride p-Bromobcnzyl bromidem-Nitrobenzyl chloride pNitrobenzyl chloride p-Cyanobenzyl chloride2,6-difluorobenzyl chloride 2,4-dibromobenzyl bromide 2,4-difiuorobcnzylchloride 2-bromo-4-nitrobenzyl bromide 3,5-difluorobenzyl chlorideo-Fluorobenzyl chloride p-Fluorobenzyl chloride2,6-dichloro-4-fiuorobenzyl chloride I 2-fluoro-4-trifiuoromethylbenzylchloride 4-fiuoro-3-trifluoromethylbenzyl chloride wMethylbenzylchloride i a-Ethylbenzyl chloride V.

a-Methyl-p-chlorobenzyl chloride a-Methyl-p-fiuorobenzyl chloridea-Methyl-p-nitrobenzyl chloride u-Methyl-2,4-difiuorobenzyl chloridea-Methyl-p-trifiuoromethylbenzyl chloride J v u-Methyl-p-bromobenzylbromide.

'EXAMPLE 17 I n When the procedure of Example 16 is followed,'ut'ptrifiuoromethylbnzyl chloride is replacedby thefbenzyl 5 halides ofTable I, Example 16 and the tertiary phosphihe is selected from Examples2, 3, 4,5,1'0;';11, 2;gfia,;

then the corresponding phosphonium saltj is prepar d; A

representative list of the phosphonium salts prgparediis shown in'ltableI, below.

TABLE I Diisoamylphenylbenzylphosphonium chloride K Di Z-methyll-butenylphenylbenzylphosphonium v f chloride 7 f lDicyclooctylphenylbenzylphosphonium chloride v i 24Dicycloheptylphenylbenzylphosphonium chlorideDicyclopentylphenylbenzylphosphonium chlorideDicyclohe'xylphenylberizylphosphonium chlorideDicyclohexylmethylphenylbenzylphosphonium chloride Di- 3 ,4,S-trimethylheptyl phenylbenzylphosphonium chloride I Di-(Z-propylallyl)phenylbenzylphosphoniurn chloride Di-(4-methyl-3-penten-1-yl)phenylbenzylphosphonium chlorideDi-(2-methylheptyl)phenylbenzylphosphonium chlorideDi-(3-methylheptyl)phenylbenzylphosphonium chlorideDi-(Z-ethylhexyl)phenylbenzylphosphonium chloride Di- (2,2,3,3-tetramethylbutyl) phenylbenzylphosphonium chlorideDi-(cyclooct-Z-enyl)phenylbenzylphosphonium chlorideDi-(iso-octenyl)phenylbenzylphosphonium chlorideDioctyl(p-tolyl)benzylphosphonium chloride Dioctyl (p-brornophenyl)(p-bromobenzyl) phosphonium bromide Dioctyl(p-chlorophenyl)(p-chlorobenzyl) phosphonium chloride I Dioctyl (p-nitrophenyl)(p-nitrobenzyl) phosphonium chlorideDioctyl(2,5-dimethylphenyl)benzylphosphonium chloride Dioctyl(p-methoxyphe nyl) (p-trifluorornethylbenzyl) phosphonium chloride Dioctyl (p-trifiuoromethylphenyl benzylphosphonium chloride Dio ctyl(p-trifluoromethoxyphenyl benzylphosphonium chloride CDipentyl(p-chlorophenyl)benzylphosphonium chlorideDihexyl(p-chlorophenyl)benzylphosphonium chlorideDiheptyl(p-chlorophenyl') benzylphosphonium chlorideDiisoamyl(p-chlorophenyl)benzylphosphonium chloride Di-(cyclohex-Z-enyl) (p-chlorophenyl) (p-chlorobenzyl) phosphonium chlorideDicyclooctyl(p-chlorophenyl)benzylphosphonium chloride v iDicycloheptyl(p-chlorophenyl benzylphosphonium chloride I" 3' t-Dicyclohexyl(p-chlorophenyl) (2,4-difluorobenzyl) phosphonium chloride-Dicyclohexylmethyl (p-chlorophenyl) a-methylbenzyl) .phosphoniumchlorideDiheptyl(p-tolyl)benzylphosphonium chlorideDiheptyli-pmitrophenyl')benzylphosphonium chlorideDiisoamyl(p-methoxyphenyl) (p-methoxybenzyl)phos-' phonium chloride y Y1: Dicycloheptyl(p-trifluoromethylphenyl) (p-fluorobenzyl) phosphoniumchl oride- Diisoamyl(p-methoxyphenyl)benzylphosphonium o id nemDidecyl(p-biplienyl')benzylphosphonium chloride 2 P p'-t ly)benzylphosphonium chloride 4 Di-(cyclooct-Z-enyl)(2,5-dimethylphenyl)benzylh sphoni m-chlori e Di-(cyclohex-Z-en l)(p-tolyl)benzylphosphonium Qfidfii F-f J: jsf'j a YDihexyl(p-bromophenyl)phosphonium chloride IDic-yclohegrylQ2fmethyl-v4rbromophenyl)benzylphose phoniuin chloride 1 YI Di;(isggctenybwdolyl)phosphonium chlorideprcyelooctylprriitrophenyl)benzylphosphonium chloride D dodecylupphenoxyphenyl)benzylphosphonium chlorideDicyclopentyl(p-trifluoromethoxyphenyl)phosphonium ,pchlorobiphenyl)berizylphosphonium fl -chloride, i Di-(Z-methylheptyl)(p-methoxyphenyl)benzylphos-i nivmw hl r de r Dihexylphenyl(p-trifluoromethoxybenzyl) phosphonium chloride 1Dihexylphenyl(o-trifiuoromethylbenzyl)phosphonium -ichlor ide Y aDihexylphenyl(o chlorobenzyl)phosphonium chloride 27 28 TABLEI-Continued v I I therapeutically effective amount of a compound of theCyclohexyl(3-chlorophenyl) (cyclohex-Z-enyl) formula:

benzylphosphonium chloride X I (Cyclohex-Z-enyl)(4-methoxyphenyl)benzylphosphonium L chloride I 5 I Y ICyclohexylmethyl(4 bromophenyl)(Z-methylheptyl) benzyl phosphoniumchloride I where: I I (Z-Ethylhexyl) (4-t-butylphenyl)heptylbenzylphos-I m d Y are hydrogen: HUOTQ, 1 bromo Q phonium chloride Y Ifilloromethyl; I I I Cycloheptyl(4-fiuorophenyl)isoamylbenzylphosphoniuand are 1 3 yl hePtYl, cycloamy Q F chlorida cyclohexyl, cycloheptyl orcyclooctyl; Nony1(4.i propy1pheny1)octylbenzylphosphonium R may also bebenzyl or substitutedbenzyl of the chloride formula (2-methylheptyl)(4-nitrophenyl) cycloheptylbenzyl- I R, 4

phosphonium chloride I i 15 R1Dicyclopentyl(4-chlorophenyl)benzylphosphonium I I Rl- 4311-, I

chloride Isoamyl(2,3-dichlorophenyl)cyclohexylbenzylphos- 7 R;

phonium chloride I I where: e I I Isoamyl(p-tolyl)benzylphosphomumchloride. I K1 is hydrogen or methyl R2, R3 R4, R5 and Ila-are hydrogen,fiuoro, chloro or bromo; a EXAMPLE 18 AfllS chloride, bromide or iodide.Dihexyloctylphenylphosphonium brromide 2. 'The method of claim 1 whereinthe compound is trioctylphenylphosphonium chloride. it 26 g. ofdihexyloctylphenylphosphomum chloride 1 3, The method of claim 1 whereinthe compound is triadded to 200 ml. ofa saturated aqueous soduim bromide1 h 1 h h hlo I solution. The mixture is then heated to 90, the. solidis gag g gig s 1v z the compound is UL melted ano the mixture is stirredfor 'min., cooled in heptflphenylphosphonium chlorideI I II I anice-bath and the water decanted. Another 200 ml. of 5 The methodofclaim1 wherein the compound is saturated sodium bromide solution is added andthe procyclohexylphenylphosphonium chlorida Cedure repeated The ionexchanged phosphonium 6. The method of claim 1 wherein the compound istrimide is filtered, washed with 1 liter of water followedby h l h nlphosphonium chloride. 7 2*200 Portions of hexane The Product is thenheated 7 .A method of treating "gastrointestinal hyperacidity twice with300 of distilled watel: until a melt cooled or ulceration in a human ormammal which comprises the and thefvaier decanted mturated h f dned oralor parenteral administration thereto of a therapeutit0 $12 5 tg g gsgygfia gi i ci fig gsg g thg g fiszm cally elfective amount of a compoundof the formula: plc is replaced with a solution of an appropriate saltof X Table I below, then the corresponding desired phospho- I t 1, niurnsalt of Table 11 below is obtained. IY I TABLEI 1 where/f7" I I I I I IX'andIY are hydrogen, halo or haloloweralkyl; sqdPlm'lodlde potassfum R"and'R are a 5 to 12'carbon atom member which 2 39 g z g} t may bestraightchained, or branchedand are: alkyl 0 rum n1 rae t I o rum p ospaer m 1 I E S -Wt t F g ll sw I R is loweralkyl, loweralkenyl,loweralkynyl or cyclo- 61 m e O 611203? I loweralkylloweralkyl', ISodium'acetate Sodium methanesulfonate" is chlorlisleIIybl-omiIdeIiodide, lIlIitl-atev phosphatg or sulfate. LE H t 8.Themethodofclaim7nwher'ei Dihexyloctylphenylphosphonium iodide j e X and-LY arehydrogen; fluoro, chloro, bromo 'or tri- Dihexyloctylphenylphosphoniumsulfate I I I fluoromethyl; I f I II I Dihexyloctylphenylphosphoniumnitrate 7 R and "R areamyl,'-hexyl"heptyl,octyl, cycloamyl,Dihexyloctylphenylphosphonium maleate I II I cyclohexyl, cycloheptyl orcyclooctyl;

R isa' 1owere1k3/ 1, loweralkenyl, lowerallcynyl, cycloloweralkylorcycloloweralkylloweralkyl I A is .chlo t ide bromide or iodid e. I

Dihexyloctylphenylphosphonium citratev Dihexyloctylphenylphosphoniumacetate Dihexyloctylphenylphosphonium oxalateDihexyloctylphenylphosphonium bromide Dihexyloctylphenylphosphoniumphosphate Dihexyloctylphenylphosphonium bromideDihexyloctylphenylphosphonium benzoatej I' Dihexyloctylphenylphosphoniummethanesulfonate. I

: -+Refer'ences'Cited-" I yNlTnn tSIATES P gaIliNTs j;

3,281,365,; 19219 6}. ,Moedritzer- 3,642,989 2/1972 Martinet a1.

When the appropriate phosphonium'saltis edfo r I I II I any of thecompounds of this invention, above P i E i' procedure may be used" F.Assistant Examiner We claim: I I

1 .'A method of'treating gastrointestinal hyperacidity I or ulcerationin a human or mammal which 'compr ises I the; oral or, parenteraladministration *fliereto -bf f a 21 218

